The elusive primary defect in hereditary muscular dystrophy may be amenable to identification in embryonic tissues in the absence of complicating degeneration. Since the cell surface or plamsa membrane must play a key role in myogenesis, viz. cell recognition and cell fusion, and since there has been considerable speculation that the primary defect in genetic dystrophic cells as a function of development in a well established embryonic chick breast muscle culture system. Because the phosphorylation state of membrane proteins may influence cell shape and the spatial distribution of membrane proteins, both of which appear to be important determinants of cell fusion, the composition of membrane phosphoproteins and the turnover of their phosphoryl groups will be determined during differentiation and fusion. Since erythrocytes from dystrophic patients appear to be abnormally phosphorylated in vitro, similar studies will be carried out with cultured dystrophic myogenic cells and their plasma membranes. Since a Ca ions-dependent stimulation of polyphosphoinositide metabolism occurs in a variety of fusion-dependent secretory processes, the turnover of these membrane components will be examined during myoblast fusion. In all these studies, the effects of Ca ions, which is required for fusion, and of 12-tetradecanolyphorbol-13-acetate (TPA), which has been shown to inhibit fusion, will be investigated. In addition, the mechanism by which TPA inhibits fusion will be sought through a study of its effect on other plasma membrane functions and the topography, composition and metabolic turnover of plasma membrane proteins. Finally, a comparison will be made between the membrane transport properties of normal and dystrophic myogenic cells, particularly with respect to Ca ions. It is anticipated that these studies will 1) provide a better understanding of the role of the plasma membrane in muscle cell development; 2) provide information about the primary defects(s) in genetically dystrophic muscle; and 3) provide new information on the mechanism of naturally occurring membrane fusion.